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Mantle Cell Lymphoma: Causes, Symptoms & Treatment

Mantle cell lymphoma (MCL) is a rare, aggressive type of non-Hodgkin lymphoma arising from B-lymphocytes in the mantle zone. It mainly affects older men and requires specialized oncological treatment.

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Things worth knowing about "Mantle cell lymphoma"

Mantle cell lymphoma (MCL) is a rare, aggressive type of non-Hodgkin lymphoma arising from B-lymphocytes in the mantle zone. It mainly affects older men and requires specialized oncological treatment.

What is Mantle Cell Lymphoma?

Mantle cell lymphoma (MCL) is a rare form of non-Hodgkin lymphoma, a malignant cancer of the lymphatic system. It develops from abnormal B-lymphocytes – white blood cells of the immune system – that originate in the mantle zone of lymph nodes. MCL accounts for approximately 5–7% of all non-Hodgkin lymphomas and is considered an aggressive subtype with a tendency to spread early throughout the body.

Causes and Risk Factors

The exact cause of mantle cell lymphoma is not yet fully understood. A hallmark genetic change is the chromosomal translocation t(11;14), in which genetic material is exchanged between chromosomes 11 and 14. This leads to overexpression of the protein Cyclin D1, which drives uncontrolled cell division.

Advanced age (peak incidence between the 6th and 7th decade of life)
Male sex (men are affected approximately three times more often than women)
Genetic factors and chromosomal instability
Weakened immune system (e.g., due to immunosuppression)

Symptoms

Mantle cell lymphoma often causes nonspecific symptoms that can also occur in other types of lymphoma. Typical symptoms include:

Painless lymph node swelling, particularly in the neck, armpits, or groin
B-symptoms: unexplained fever, heavy night sweats, and unintentional weight loss (more than 10% of body weight within 6 months)
Enlargement of the spleen (splenomegaly) and liver (hepatomegaly)
Fatigue and general weakness
In advanced stages: involvement of the bone marrow, blood, or gastrointestinal tract

Diagnosis

Diagnosing mantle cell lymphoma requires several diagnostic steps:

Tissue Biopsy and Histology

Diagnosis is primarily established through a lymph node or tissue biopsy. The removed tissue is examined under a microscope to identify the characteristic lymphoma cells.

Immunohistochemistry and Molecular Diagnostics

Using immunohistochemistry, the overexpression of Cyclin D1 and the presence of the surface marker CD5 are confirmed. The translocation t(11;14) can be verified by fluorescence in situ hybridization (FISH) or molecular genetic methods.

Staging and Further Investigations

Blood count and laboratory tests (LDH, beta-2 microglobulin)
Bone marrow biopsy to assess bone marrow involvement
Computed tomography (CT) or PET-CT for staging
Gastroscopy and colonoscopy if gastrointestinal involvement is suspected

Treatment

Treatment of mantle cell lymphoma depends on the stage of the disease, the age and general condition of the patient, and the risk profile determined by the MIPI score (Mantle Cell Lymphoma International Prognostic Index).

First-line Therapy in Younger, Fit Patients

For younger and physically fit patients, intensive immunochemotherapy is usually the goal, often using the R-CHOP or R-DHAP regimen, followed by autologous stem cell transplantation to consolidate the response.

First-line Therapy in Older Patients

For older or less fit patients, less intensive regimens are preferred, such as R-CHOP or BR (bendamustine plus rituximab), often followed by maintenance therapy with rituximab.

Targeted Therapies

In the case of relapse or refractory disease, more modern targeted agents are available:

Ibrutinib and Acalabrutinib (BTK inhibitors): Block a key signaling pathway in lymphoma cells
Venetoclax: A BCL-2 inhibitor that promotes programmed cell death in tumor cells
CAR-T cell therapy (e.g., Brexucabtagene autoleucel): An innovative immunotherapy for patients after multiple prior treatments

Prognosis

Mantle cell lymphoma often shows a good initial response to therapy but has a tendency to relapse. Median survival has improved significantly with modern therapies and is now 5–10 years or longer for many patients. A small proportion of patients follow an indolent (slow-growing) course that does not require immediate treatment.

References

Dreyling M. et al. - Mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 2017.
Swerdlow S.H. et al. (eds.) - WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition, IARC Press, Lyon, 2017.
Vose J.M. - Mantle cell lymphoma: 2017 update on diagnosis, risk-stratification, and clinical management. American Journal of Hematology, 2017.

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